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银屑病皮损中白细胞介素-17亚型及受体的特征分析

Characterization of the interleukin-17 isoforms and receptors in lesional psoriatic skin.

作者信息

Johansen C, Usher P A, Kjellerup R B, Lundsgaard D, Iversen L, Kragballe K

机构信息

Department of Dermatology, Aarhus University Hospital, DK-8000 Aarhus C, Denmark.

出版信息

Br J Dermatol. 2009 Feb;160(2):319-24. doi: 10.1111/j.1365-2133.2008.08902.x. Epub 2008 Oct 21.

Abstract

BACKGROUND

Th17 cells are a lineage of proinflammatory T helper cells producing interleukin (IL)-17. The importance of Th17 cells in inflammation and autoimmunity has now been recognized. The IL-17 cytokine family consists of six isoforms (IL-17A-IL-17F) whereas five members of the IL-17 receptor (IL-17R) family have been identified (IL-17RA-IL-17RE).

OBJECTIVES

To characterize the expression of the IL-17 isoforms and receptors in lesional and nonlesional psoriatic skin. Methods Keratome and punch biopsies taken from patients with psoriasis were examined by enzyme-linked immunosorbent assay and quantitative reverse transcription-polymerase chain reaction in order to measure the IL-17 isoforms and receptors.

RESULTS

We demonstrated significantly increased mRNA expression of IL-17A, IL-17C and IL-17F in psoriatic skin. In contrast, the mRNA expression of IL-17B and IL-17D was significantly decreased in lesional compared with nonlesional skin, while IL-17E mRNA was undetectable. The increased mRNA expression of IL-17A, IL-17C and IL-17F was paralleled by an increased protein accumulation of these cytokines in psoriatic skin. Analysis of the IL-17R mRNA expression revealed significantly impaired mRNA expression of IL-17RB, IL-17RC, IL-17RD and IL-17RE in lesional psoriatic skin, whereas the mRNA expression of IL-17RA was similar in lesional and nonlesional psoriatic skin.

CONCLUSIONS

This study characterizes the mRNA profile of the IL-17 isoforms and receptors in psoriatic skin lesions. Furthermore, we demonstrate for the first time augmented protein levels of IL-17A, IL-17C and IL-17F in psoriatic skin lesions, indicating a possible role for IL-17C in addition to IL-17A and IL-17F in the pathogenesis of psoriasis.

摘要

背景

Th17细胞是一类产生白细胞介素(IL)-17的促炎性辅助性T细胞谱系。目前已认识到Th17细胞在炎症和自身免疫中的重要性。IL-17细胞因子家族由六种异构体(IL-17A - IL-17F)组成,而IL-17受体(IL-17R)家族已鉴定出五个成员(IL-17RA - IL-17RE)。

目的

明确银屑病皮损和非皮损皮肤中IL-17异构体和受体的表达特征。方法 采用酶联免疫吸附测定和定量逆转录-聚合酶链反应检测银屑病患者的角膜刀活检和钻孔活检组织,以测定IL-17异构体和受体。

结果

我们发现银屑病皮肤中IL-17A、IL-17C和IL-17F的mRNA表达显著增加。相比之下,与非皮损皮肤相比,皮损中IL-17B和IL-17D的mRNA表达显著降低,而未检测到IL-17E的mRNA。IL-17A、IL-17C和IL-17F mRNA表达的增加与这些细胞因子在银屑病皮肤中蛋白质积累的增加平行。对IL-17R mRNA表达的分析显示,银屑病皮损中IL-17RB、IL-17RC、IL-17RD和IL-17RE的mRNA表达显著受损,而IL-17RA在银屑病皮损和非皮损皮肤中的mRNA表达相似。

结论

本研究明确了银屑病皮肤病变中IL-17异构体和受体的mRNA谱。此外,我们首次证明银屑病皮肤病变中IL-17A、IL-17C和IL-17F的蛋白质水平升高,表明除IL-17A和IL-17F外,IL-17C在银屑病发病机制中可能也发挥作用。

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